Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Resultados 1 - 4 de 4
Filtrar
Más filtros

Banco de datos
Tipo del documento
Publication year range
1.
Clin Dev Immunol ; 2013: 287469, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24454471

RESUMEN

Prolactin (PRL) plays an important role in modulating the immune response. In B cells, PRL enhances antibody production, including antibodies with self-specificity. In this study, our aims were to determine the level of PRL receptor expression during bone-marrow B-cell development and to assess whether the presence of high PRL serum concentrations influences absolute numbers of developing populations and disease outcome in lupus-prone murine models. We observed that the PRL-receptor is expressed in early bone-marrow B-cell; the expression in lupus-prone mice, which had the highest level of expression in pro-B cells and immature cells, differed from that in wild-type mice. These expression levels did not significantly change in response to hyperprolactinemia; however, populations of pro-B and immature cells from lupus-prone strains showed a decrease in the absolute numbers of cells with high PRL-receptor expression in response to PRL. Because immature self-reactive B cells are constantly being eliminated, we assessed the expression of survival factor BIRC5, which is more highly expressed in both pro-B and immature B-cells in response to PRL and correlates with the onset of disease. These results identify an important role of PRL in the early stages of the B-cell maturation process: PRL may promote the survival of self-reactive clones.


Asunto(s)
Linfocitos B/inmunología , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/metabolismo , Prolactina/metabolismo , Animales , Anticuerpos Antinucleares/inmunología , Linfocitos B/metabolismo , Modelos Animales de Enfermedad , Femenino , Hiperprolactinemia/genética , Hiperprolactinemia/inmunología , Hiperprolactinemia/metabolismo , Inmunofenotipificación , Proteínas Inhibidoras de la Apoptosis/genética , Proteínas Inhibidoras de la Apoptosis/metabolismo , Lupus Eritematoso Sistémico/genética , Recuento de Linfocitos , Ratones , Ratones Endogámicos MRL lpr , Prolactina/sangre , Receptores de Prolactina/metabolismo , Proteínas Represoras/genética , Proteínas Represoras/metabolismo , Survivin
2.
Cells ; 10(2)2021 02 04.
Artículo en Inglés | MEDLINE | ID: mdl-33557010

RESUMEN

Self-reactive immature B cells are eliminated through apoptosis by tolerance mechanisms, failing to eliminate these cells results in autoimmune diseases. Prolactin is known to rescue immature B cells from B cell receptor engagement-induced apoptosis in lupus-prone mice. The objective of this study was to characterize in vitro prolactin signaling in immature B cells, using sorting, PCR array, RT-PCR, flow cytometry, and chromatin immunoprecipitation. We found that all B cell maturation stages in bone marrow express the prolactin receptor long isoform, in both wild-type and MRL/lpr mice, but its expression increased only in the immature B cells of the latter, particularly at the onset of lupus. In these cells, activation of the prolactin receptor promoted STAT3 phosphorylation and upregulation of the antiapoptotic Bcl2a1a, Bcl2l2, and Birc5 genes. STAT3 binding to the promoter region of these genes was confirmed through chromatin immunoprecipitation. Furthermore, inhibitors of prolactin signaling and STAT3 activation abolished the prolactin rescue of self-engaged MRL/lpr immature B cells. These results support a mechanism in which prolactin participates in the emergence of lupus through the rescue of self-reactive immature B cell clones from central tolerance clonal deletion through the activation of STAT3 and transcriptional regulation of a complex network of genes related to apoptosis resistance.


Asunto(s)
Prolactina/metabolismo , Factor de Transcripción STAT3/metabolismo , Animales , Apoptosis , Ratones , Ratones Endogámicos MRL lpr
3.
J Immunol Res ; 2021: 6630715, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33763492

RESUMEN

Systemic lupus erythematosus is characterized by high levels of IgG class autoantibodies that contribute to the pathophysiology of the disease. The formation of these autoantibodies occurs in the germinal centers, where there is cooperation between follicular T helper cells (TFH) and autoreactive B cells. Prolactin has been reported to exacerbate the clinical manifestations of lupus by increasing autoantibody concentrations. The objective of this study was to characterize the participation of prolactin in the differentiation and activation of TFH cells, by performing in vivo and in vitro tests with lupus-prone mice, using flow cytometry and real-time PCR. We found that TFH cells express the long isoform of the prolactin receptor and promoted STAT3 phosphorylation. Receptor expression was higher in MRL/lpr mice and correlative with the manifestations of the disease. Although prolactin does not intervene in the differentiation of TFH cells, it does favor their activation by increasing the percentage of TFH OX40+ and TFH IL21+ cells, as well as leading to high serum concentrations of IL21. These results support a mechanism in which prolactin participates in the emergence of lupus by inducing overactive TFH cells and perhaps promoting dysfunctional germinal centers.


Asunto(s)
Centro Germinal/inmunología , Interleucinas/metabolismo , Lupus Eritematoso Sistémico/inmunología , Nefritis Lúpica/inmunología , Prolactina/metabolismo , Receptores OX40/metabolismo , Linfocitos T Colaboradores-Inductores/inmunología , Animales , Autoanticuerpos/metabolismo , Células Cultivadas , Modelos Animales de Enfermedad , Humanos , Ratones , Ratones Endogámicos MRL lpr , Receptores OX40/genética , Receptores de Prolactina/metabolismo , Factor de Transcripción STAT3/metabolismo , Regulación hacia Arriba
4.
J Immunol Res ; 2016: 3219017, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27314053

RESUMEN

Prolactin has an immunomodulatory effect and has been associated with B-cell-triggered autoimmune diseases, such as systemic lupus erythematosus (SLE). In mice that develop SLE, the PRL receptor is expressed in early bone marrow B-cells, and increased levels of PRL hasten disease manifestations, which are correlated with a reduction in the absolute number of immature B-cells. The aim of this work was to determine the effect of PRL in an in vitro system of B-cell tolerance using WEHI-231 cells and immature B-cells from lupus prone MRL/lpr mice. WEHI-231 cells express the long isoform of the PRL receptor, and PRL rescued the cells from cell death by decreasing the apoptosis induced by the cross-linking of the B-cell antigen receptor (BCR) as measured by Annexin V and active caspase-3. This decrease in apoptosis may have been due to the PRL and receptor interaction, which increased the relative expression of antiapoptotic Bcl-xL and decreased the relative expression of proapoptotic Bad. In immature B-cells from MRL/lpr mice, PRL increased the viability and decreased the apoptosis induced by the cross-linking of BCR, which may favor the maturation of self-reactive B-cells and contribute to the onset of disease.


Asunto(s)
Apoptosis , Células Precursoras de Linfocitos B/citología , Células Precursoras de Linfocitos B/metabolismo , Prolactina/metabolismo , Receptores de Antígenos de Linfocitos B/metabolismo , Animales , Apoptosis/efectos de los fármacos , Apoptosis/genética , Apoptosis/inmunología , Caspasa 3/metabolismo , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/inmunología , Expresión Génica , Ratones , Ratones Endogámicos MRL lpr , Células Precursoras de Linfocitos B/efectos de los fármacos , Prolactina/farmacología , Unión Proteica , Receptores de Prolactina/genética , Receptores de Prolactina/metabolismo
SELECCIÓN DE REFERENCIAS
Detalles de la búsqueda